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Biomedical subjects

V Barbieri

Publications and source records attributed to V Barbieri.

At least 19 recordsLinked to original sources

Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance.

AIMS: Pancreatic adenocarcinoma is an aggressive gastrointestinal malignancy with only a few long-term survivors even after radical surgery. Patients with ampullary cancer have a better prognosis but adjuvant therapy needs further improvement. Epithelial cell adhesion molecule (Ep-CAM) is strongly expressed in a variety of epithelial cancers and represents a promising target for immunological tumour therapy. Thus, the aim of this study was to investigate Ep-CAM expression and its potential prognostic impact in pancreatic and ampullary carcinomas. METHODS: Ep-CAM expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series of consecutive patients with pancreatic (n = 153) and ampullary cancer (n = 34). RESULTS: Ep-CAM overexpression was observed in 85 of 153 pancreatic cancer specimens (56%) and in 29 of 34 ampullary cancer samples (85%). Overall, Ep-CAM failed to be an independent prognostic marker. However, subgroup analyses showed that Ep-CAM overexpression correlated with shorter overall survival among patients with ampullary cancer and advanced stage pancreatic cancer. In the latter subgroup, survival gradually worsened with increasing Ep-CAM scores. Furthermore, in ampullary cancer, Ep-CAM overexpression was found to correlate with tumour stage. CONCLUSIONS: Ep-CAM overexpression was detectable in the majority of cases with pancreatic and ampullary cancer. Therefore, Ep-CAM represents an attractive target for immune-based therapeutic interventions in these tumour entities. However, the prognostic value of Ep-CAM overexpression remains undetermined.

Adenocarcinoma↗

Theory of Mind in schizophrenia: first person vs third person perspective.

Patients suffering from schizophrenia have an impaired meta-representation also known as Theory of Mind (ToM). Moreover, the presence of delusions or other positive symptoms of schizophrenia has been correlated to poor ToM performances. Lack of insight is a common symptom of schizophrenia and can be considered a critical manifestation of impaired ToM abilities. In particular, the present study addresses the role of perspective ToM ability in schizophrenic patients. Thirty severely delusional schizophrenic patients completely lack insight when interviewed about their delusions. Seven subsequently gain insight about their mental state when perspective is shifted from the first person to third person. These data suggest that in some delusional schizophrenic patients, it may be possible to gain access to and modify their mental states.

Adult↗

An oncologist-based model of cancer genetic counselling for hereditary breast and ovarian cancer.

BACKGROUND: We describe a multistep model of cancer genetic counselling designed to promote awareness, and disease surveillance and preventive measures for hereditary and familial breast and ovarian cancer. PATIENTS AND METHODS: Step T0 of the model entails information giving; this is followed by pedigree analysis and risk estimation (T1), risk communication and genetic testing (T2), and genetic test result communication (T3). User consent was required to proceed from one step to the next. Surveillance and preventive measures are proposed to at-risk users. Of the 311 subjects who requested cancer genetic counselling, consent data to each counselling step were available for 295: 93 were disease-free, 187 had breast cancer, 12 had ovarian cancer and three had breast plus ovarian cancer. RESULTS: Consent was high at T0 (98.39%), T1 (96.40%) and T2 (99.65%). Consent decreased at the crucial points of counselling: T2 (87.71%) and T3 [genetic test result communication (85.08%), and extension of counselling to and testing of relatives (65.36%)]. CONCLUSIONS: The model fosters the user's knowledge about cancer and favours identification of at-risk subjects. Furthermore, by promoting awareness about genetic testing and surveillance measures, the algorithm enables users to make a fully informed choice of action in case of predisposing or familial cancer risk.

Breast Neoplasms↗

Fourteen-year experience with imported malaria.

Geographical position, an increasing flow of immigrants and refugees coming from regions where malaria is endemic might further increase those cases of malaria imported to Calabria due to travel on military missions, visiting relatives, business and leisure. However, few reports have been published regarding malaria imported into the southern Italian region of Calabria. Based on data from our laboratory, official reports received from the Italian Ministry of Health and Regional Health Offices, an epidemiological analysis of malaria cases registered in Calabria from January 1988 to December 2001 is reported. The epidemiological and clinical features concerning the cases are discussed. A total of 34 slide-confirmed malaria cases were observed in Calabria during the period in question. Infections were mostly acquired in Africa (84.8%), while remaining infections came from Asia (9.1%) and South America and Europe (6.0%). Length of stay in the endemic area did not increase the infection risk. Etiological diagnosis indicated Plasmodium falciparum as the species most often involved (60.6%), followed by Plasmodium vivax (36.3%) and P. vivax/Plasmodium malariae mixed infection (3.0%). The mortality rate was about 3.0%. The number of cases during the second seven-year period of this study was almost double that of the first seven-year period. Correct chemoprophylaxis was performed by only 27.3% of our studied subjects. Delay of malaria diagnosis ranged between 4 days and 1 month. In conclusion, increases in malaria cases, mostly due to P. falciparum, delay in diagnosis and reporting to the Regional Health Office, as well as the increasing arrival of refugees from endemic areas, are epidemiological concerns in Calabria, the southernmost region of continental Italy.

Adult↗

BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells.

Germline mutations of the tumour suppressor gene BRCA1 are involved in the predisposition and development of breast cancer and account for 20-45% of all hereditary cases. There is an increasing evidence that these tumours are characterised by a specific phenotype and pattern of gene expression. We have hypothesised that differences in chemosensitivity might parallel molecular heterogeneity of hereditary and sporadic breast tumours. To this end, we have investigated the chemosensitivity of the BRCA1-defective HCC1937 breast cancer cell line, and the BRCA1-competent MCF-7 (hormone-sensitive) and MDA-MB231 (hormone-insensitive) breast cancer cell lines using the MTT assay. The 50% inhibitory concentration (IC(50)) for the individual compounds were derived by interpolate plot analysis of the logarithmic scalar concentration curve after a 48 h exposure. HCC1937 cells were significantly (P<0.005) more sensitive to cisplatin (CDDP) (IC(50) : 30-40 microM) compared with MCF-7 (IC(50) : 60-70 microM) and MDA-MB231 (IC(50) : 90-100 microM) cells. On the other hand, BRCA1-defective breast cancer cells were significantly less sensitive to doxorubicin (Dox) (IC(50) : 45-50 microM) compared with MCF-7 (IC(50) : 1-5 microM) and MDA-MB231 (IC(50) : 5-10 microM) (P<0.02), as well as to paclitaxel (Tax) (IC(50) : >2 microM for HCC1937, 0.1-0.2 microM for MCF-7 and 0.01-0.02 microM for MDA-MB231) (P<0.001). Full-length BRCA1 cDNA transfection of BRCA1-defective HCC1937 cells led to the reconstituted expression of BRCA1 protein in HCC1937/(WT)BRCA1-derived cell clone, but did not reduce tumour cell growth in soft agar. BRCA1 reconstitution reverted the hypersensitivity to CDDP (P<0.02), and restored the sensitivity to Dox (P<0.05) and Tax (P<0.001), compared with parental HCC1937 cells. Taken together, our findings suggest a specific chemosensitivity profile of BRCA1-defective cells in vitro, which is dependent on BRCA1 protein expression, and suggest prospective preclinical and clinical investigation for the development of tailored therapeutical approaches in this setting.

Antineoplastic Agents↗

Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer.

Several genes have been involved in the pathogenesis of hereditary breast/ovarian cancer (BOC), but mutations in the BRCA1 gene are by far the most recurrent. In this study, we report the identification of a founder mutation in a geographically and historically homogeneous population from Calabria, a south Italian region. A screening performed on 24 patients from unrelated families highlighted the high prevalence of a 5083del19 alteration in the BRCA1 gene, which accounts for 33% of the overall gene mutations. The same mutation was also detected in 4 patients, all of Calabrian origin, referred to us by research centres from the north of Italy. Allelotype analysis, performed on probands and unaffected family members revealed the presence a common allele, therefore suggesting a founder effect due to a common ancestor. Our findings underscore the importance of ethnic background homogeneity in patients' selection and highlight the usefulness of founder mutations as a potential tool for optimisation of preclinical diagnosis in gene carriers and therapeutic approaches in affected individuals.

Adult↗

Hereditary nonpolyposis coloretal cancer: identification of novel germline mutations in two kindreds not fulfulling the Amsterdam criteria. Mutations in brief no. 203. Online.

Hereditary nonpolyposis colon cancer results from heritable defects in the MLH1, MSH2, PMS1 and PMS2 genes, which encode proteins involved in the mismatch repair process. In this work we report the identification of two novel germline mutations in the MLH1 gene from two unrelated HNPCC families. The two affected families do not fulfill the Amsterdam criteria. In family 1 we found a missense S93G mutation, which lies in a MLH1 domain critical for its MMR functions. In family 2 we found a two nucleotide insertion (AG) in position 523 from the AUG which determines an early stop codon at position 606 (codon 203). In both families the mutant alleles cosegregate with the cancer phenotype.

Adaptor Proteins, Signal Transducing↗

Identification by differential display of transcripts regulated during hematopoietic differentiation.

The polymerase chain reaction-based differential display method (DDRT-PCR) was used to identify mRNAs differentially expressed during the maturation of human CD34+ progenitor cells stimulated to differentiate in vitro towards granulomonocytic or erythroid lineages with a mixture of hemopoietins (kit ligand + interleukin 3 + GM-CSF in the absence or presence of erythropoietin, respectively). Three cDNA transcripts (B32, B41, and B56) display differential expression during cytokine-induced maturation of CD34+ cells. These clones have no homology with already-described sequences. Primer extension cofirmed the presence of the corresponding mRNA. The levels of mRNA corresponding to B32 are enhanced in the later phases of the granulomonocytic as well as in the erythroid differentiation of CD34+ cells. The mRNA identified by B41 was induced by a late stage in only granulomonocytic differentiation of CD34+ cells. The mRNA corresponding to B56 was instead present in nonstimulated CD34+ cells, declined in the early stages of differentiation, and reappeared at later stages in cells treated with both combinations of cytokines. Expression of these genes was detected in a number of acute myelogenous leukemias, as well as in some leukemic cell lines. B32 and B41 were downregulated in KG-1 cells induced to differentiate towards the monocytic lineage, whereas the levels of B56 were unchanged. In K562 cells, clones B41 and B56 were downregulated only in the late phases of PMA-induced megakaryocytic differentiation and during erythroid differentiation. B32 was rapidly downregulated when K562 cells were induced to differentiate towards either megakaryocytic or erythroid phenotypes. These transcripts represent novel hematopoietic cDNAs that should prove of value for the study of human blood cells and their disorders.

Antigens, CD34↗

CD36 is rapidly and transiently upregulated on phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes. Analysis by a new monoclonal antibody (UN7).

The monoclonal antibody (mAb) UN7, clustered as an anti-CD36 mAb, has been used to test the cell surface expression of CD36 on peripheral blood lymphocytes (PBL) following mitogenic stimulation. CD36, scarcely expressed on resting cell membranes, was rapidly upregulated on PBL after phytohemagglutinin (PHA) stimulation. The antigen was detected on the cell surface after 15 min of stimulation, increased rapidly by 60 min and peaked between 3 and 12 h, declining thereafter. The inhibition of protein synthesis by cycloheximide did not modify the PHA-induced expression of CD36. Neither the anti-CD3 OKT3 mAb nor the anti-CD2 BIL 2.29 and 9.1 mAbs induced any significant upregulation of the molecule. The addition of anti-CD28 15E8 mAb or IL-2 or IFN-gamma to PHA or anti-CD3 or anti-CD2 mAbs did not influence the pattern of CD36 expression. The phorbol-2-myristate-13-acetate (PMA), alone or in combination with ionomycin, was unable to activate the expression of CD36, while it inhibited the PHA-induced upregulation. The PHA-induced upregulation of CD36 was partially inhibited by the addition of LY294002 or wortmannin, while not affected by that of calphostin C. Thus, CD36 was found to be early and transiently upregulated by PHA stimulation on PBL. The rapid modulation of the molecule was not related to new protein synthesis, but was probably due to the insertion into the plasma membrane of a presynthetized protein pool.

Antibodies, Monoclonal↗

Inflammatory pseudotumour of the lung presenting as an airway obstructive syndrome.

The inflammatory pseudotumour of the lung is a rare and non-malignant neoplasm, which can be asymptomatic or characterized by variable clinical expressions. This report refers to a case occurring in a young woman and presenting as a persistent airway obstructive syndrome. With regard to histopathologic characterization, the present case can be classified as a fibrous histiocytic subtype.

Adult↗

Serum neuron-specific enolase in various pathological conditions.

Quantitative determination of neuron-specific enolase in the serum was performed by RIA method in 18 neurological patients and in 22 patients with pulmonary diseases. The data confirmed that the specificity of this marker is not absolute for the detection both of the nature and of the seat of origin of the disease. Further problems are posed in patients which simultaneously suffer from endocrine, nervous and pulmonary abnormality.

Adolescent↗